Novel Methods to Predict Outcome Using Neuroimaging

Novel Methods to Predict Outcome Using Neuroimaging

The capacity of cognitive neuroscience to inform clinical practice has stimulated both excitement and controversy.1-5 Noninvasive brain imaging methods are providing unprecedented views of the structural and functional development and aging of an individual's brain or state of brain pathology. These exciting new views of maturing and aging brains or of brain pathology may provide novel information relevant to the enhancement of clinical practice. The implications of neuroscience for clinical practice, however, have raised some controversy because of speculative and potentially flawed interpretations created by associating animal experimentation with human medical practice.1 As a result, the relationship between clinical practice and neuroscience has been called "a bridge too far."6 Nonetheless, it is evident that the field of cognitive neuroscience holds promise to inform clinical practice. The promise lies in its potential to address critical issues such as:

Understanding the neural processes underlying the development of essential skills, such as reading and numeracy, and the "healthy" decline of cognitive functions such as memory.

Understanding the pathophysiology of various neuropsychiatric disorders.

Assessment and prediction of interventional outcome.

Early identification of persons at risk for neuropsychiatric disorders.

While the following discussion focuses mainly on reading skills and disabilities, similar arguments may be applied to clinical issues. We focus on recent findings from our laboratory that highlight the extent to which functional and structural neuroimaging techniques can serve as a clinically useful tool in predicting outcome.

Reading is a skill that is undeniably critical to success in modern society, yet the development of reading abilities in children is becoming a significant problem. Based on the National Assessment of Educational Progress,7 only 31% of the nation's fourth graders are performing at or above the proficient achievement level that demonstrates solid academic performance in reading. Furthermore, dyslexia, a developmental learning disability that is characterized by difficulty in reading in individuals who otherwise have the intelligence and necessary motivation for accurate and fluent reading,8 is prevalent in 5% to 17% of all children and 80% of children with learning disabilities.9

Reading First, an initiative under the No Child Left Behind Act of 2002, was enacted with the goal of achieving high reading proficiency by the end of the third grade by 2014. The initiative emphasizes early identification of children who are at risk for reading failure. Once they are identified, neuroscientifically proven reading programs, interventions, and strategies in the early grades are used to improve reading fluency.

Neuroscientific evidence

Neuroscientific evidence from a number of brain imaging studies performed over the past decade has provided us with novel insights into our knowledge of normal and disturbed reading.10-13 These studies have demonstrated that reading activates a widely distributed set of areas in the occipitotemporal; posterior temporal to parietotemporal; precentral; and inferior frontal gyri, which sustain orthographic, semantic, and phonologic processing.14 It has also been shown that the left posterior superior temporal, parietotemporal, and occipitotemporal regions are dysfunctional--with abnormal increases in activation in the left frontal region--in dyslexic readers.15-18 These findings have implications for novel models of reading and the disabilities associated with it.

Recent studies have shown the effects of interventions on neural patterns in response to reading.19-22 These studies demonstrate normalization of brain activation in the left hemispheric regions, which is critical for reading and generally dysfunctional in persons with dyslexia. In addition, an increased activation in the homologous right hemispheric regions is found in dyslexic brains after intervention. These studies provide insights into plastic changes that could occur in regions related to normal reading as well as putative compensatory changes in response to successful intervention. If examined carefully and with a larger number of subjects, these studies have the potential to assign optimal intervention strategies to children with different behavioral and neural profiles.

Investigation of the extent to which neuroimaging techniques can serve as a clinically useful tool in predicting future reading skills is still in its infancy. There are only a few developmental studies predicting reading skills and language, all of which use event-related potentials.23-25 Another study examining brain morphology using voxel-based morphometry (VBM) predicted short-term learning of novel speech sounds in adults.26 While there have been no studies that used functional neuroimaging to predict outcome in reading, there are an increasing number of studies with functional imaging in disorders such as depression27-29 or Alzheimer disease.30-33